DPP-IV inhibitors inhibit inactivation of glucagon-like peptide-1 (hereinafter to be referred to as GLP-1) in plasma, and potentiate their incretin action. Therefore, they are useful as therapeutic drugs for diabetes and the like, and under research and development as drugs potentially effective for the treatment of diabetes, particularly type 2 diabetes (see, patent references 1 to 6, non-patent reference 1).
A series of compounds have been reported as useful thiazolidine derivatives. (see, patent reference 7). Of the Example compounds described in this reference, 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine is noteworthy (hereinafter to be referred to as compound I). While compound I is described in the form of a 3 hydrochloride, this salt has pharmaceutically undesirable properties from the aspects of stability and hygroscopicity, and production in the same form with reproducibility has been found to be difficult. Particularly, to satisfy the regulatory requirements in the development of pharmaceutical products, a compound of certain quality needs to be produced with reproducibility. Therefore, these properties observed in 3 hydrochloride of compound I are considered to be disadvantageous for the development of pharmaceutical products.
Moreover, while this reference (patent reference 7) discloses particular salts of “compound I” and other thiazolidine derivatives as Example compounds, no discussion is found over a polymorphic crystal of any of the Example compounds.
An ability of a substance to crystallize into two or more kinds of crystal structures is known as polymorphism, and individual crystal forms are called polymorphic crystal. Various polymorphic crystals of a single compound sometimes show completely different properties of preservation stability, solubility and the like. Such difference in the properties may result in the difference in the action effect. In view of such differences, study of individual polymorphic crystals and a mixture of polymorphic crystals is particularly useful for the development of pharmaceutical products.
There are multiple notations of polymorphic crystals depending on the nomenclature, such as Form A, Form B, Form I, Form II, Form α, Form β and the like. In these notations, “Type” (Type A etc.) may be used instead of “Form”. In any event, both notations are used to mean the same.
However, it is not always easy to find various polymorphic crystals of a certain compound. Once the presence of a particular polymorphic crystal is acknowledged and the characteristics thereof are considered to be preferable, the workers need to find a method to always supply the polymorphic crystal constantly in a large amount as single crystals. It is not easy to establish a method of supplying a single crystal or substantially single crystal of a certain polymorphic crystal, and intensive studies are required.    Patent reference 1: WO97/040832    Patent reference 2: WO98/019998    Patent reference 3: U.S. Pat. No. 5,939,560    Patent reference 4: WO01/055105    Patent reference 5: WO02/002560    Patent reference 6: WO02/062764    Patent reference 7: WO02/014271    Non-patent reference 1: J. Med. Chem., 47(17), 4135-4141 (2004)